Porfimer Sodium
FDA Drug Information • Also known as: Photofrin
- Brand Names
- Photofrin
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION, POWDER, FOR SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Porfimer sodium is a photoactivated radical generator. Porfimer sodium is a mixture of oligomers formed by ether and ester linkages of up to eight porphyrin units. The structural formula below is representative of the components of porfimer sodium. PHOTOFRIN (porfimer sodium) for injection, for intravenous use, is supplied in a single-dose vial as dark red to reddish brown lyophilized powder, which has a cake-like appearance. Each vial contains 75 mg of porfimer sodium. Hydrochloric acid and/ or sodium hydroxide may be added to adjust the pH to within 7.2-7.9. There are no preservatives or other additives. Porfimer sodium Chemical Formula
What Is Porfimer Sodium Used For?
1 INDICATIONS AND USAGE PHOTOFRIN is a photoactivated radical generator indicated for: Esophageal Cancer ( 1.1 ) Palliation of patients with completely obstructing esophageal cancer, or of patients with partially obstructing esophageal cancer who, in the opinion of their physician, cannot be satisfactorily treated with Nd:YAG laser therapy Endobronchial Cancer ( 1.2 ) Treatment of microinvasive endobronchial non-small-cell lung cancer (NSCLC) in patients for whom surgery and radiotherapy are not indicated Reduction of obstruction and palliation of symptoms in patients with completely or partially obstructing endobronchial NSCLC High-Grade Dysplasia in Barrett’s Esophagus ( 1.3 ) Ablation of high-grade dysplasia (HGD) in Barrett’s esophagus (BE) patients who do not undergo esophagectomy 1.1 Esophageal Cancer PHOTOFRIN ® is indicated for the palliation of patients with completely obstructing esophageal cancer, or of patients with partially obstructing esophageal cancer who, in the opinion of their healthcare provider, cannot be satisfactorily treated with Nd:YAG laser therapy. 1.2 Endobronchial Cancer PHOTOFRIN is indicated for the treatment of microinvasive endobronchial non-small-cell lung cancer (NSCLC) in patients for whom surgery and radiotherapy are not indicated. PHOTOFRIN is indicated for the reduction of obstruction and palliation of symptoms in patients with completely or partially obstructing endobronchial NSCLC. 1.3 High-Grade Dysplasia in Barrett’s Esophagus PHOTOFRIN is indicated for the ablation of high-grade dysplasia in Barrett’s esophagus patients who do not undergo esophagectomy.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION PHOTOFRIN ( 2.1 ) PHOTOFRIN administration: 2 mg/kg intravenous Photoactivation ( 2.2 ) Esophageal Cancer Laser light dose of 300 J/cm of fiber optic diffuser length 40–50 hours following injection with PHOTOFRIN; repeated, if needed, 96-120 hours after initial injection Endobronchial Cancer Laser light dose of 200 J/cm of fiber optic diffuser length 40–50 hours following injection with PHOTOFRIN; repeated, if needed, after gentle debridement of residual tumor 96-120 hours after initial injection High-Grade Dysplasia in Barrett’s Esophagus Laser light dose of 130 J/cm of fiber optic diffuser length 40–50 hours following injection with PHOTOFRIN; repeated, if needed, with a light dose of 50 J/cm of fiber optic diffuser length 96-120 hours after initial injection 2.1 Important Administration Instructions Photodynamic therapy (PDT) with PHOTOFRIN is a two-stage process requiring administration of both drug and light. The first stage of PDT is the intravenous injection of PHOTOFRIN at 2 mg/kg. Illumination with laser light 40–50 hours following injection with PHOTOFRIN constitutes the second stage of therapy. A second laser light application may be given 96-120 hours after injection [ see Dosage and Administration ( 2.2 )] . In clinical studies on endobronchial cancer, debridement via endoscopy was required 2-3 days after the initial light application. Standard endoscopic techniques are used for light administration and debridement. Healthcare providers should be fully familiar with the patient’s condition and trained in the safe and efficacious treatment of esophageal or endobronchial cancer, or high-grade dysplasia (HGD) in Barrett’s esophagus (BE) using PDT with PHOTOFRIN and associated light delivery devices. PDT with PHOTOFRIN should be applied only in those facilities properly equipped for the procedure. The laser system must be approved for delivery of a stable power output at a wavelength of 630 ± 3 nm. Light is delivered to the tumor by cylindrical OPTIGUIDE™ fiber optic diffusers passed through the operating channel of an endoscope/bronchoscope. Instructions for use of the fiber optic and the selected laser system should be read carefully before use. OPTIGUIDE™ cylindrical diffusers are available in several lengths. The choice of diffuser tip length depends on the length of the tumor or Barrett’s mucosa to be treated. Diffuser length should be sized to avoid exposure of nonmalignant tissue to light and to prevent overlapping of previously treated malignant tissue. Refer to the OPTIGUIDE™ instructions for use for complete instructions concerning the fiber optic diffuser. 2.2 PHOTOFRIN Recommended Dosage The recommended dosage of PHOTOFRIN is 2 mg/kg of body weight administered as a single slow intravenous injection over 3 to 5 minutes. Preparation and Administration Reconstitute each vial of PHOTOFRIN with 31.8 mL of either 5% Dextrose Injection (USP) or 0.9% Sodium Chloride Injection (USP), resulting in a final...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Gastroesophageal Fistula and Perforation [see Warnings and Precautions ( 5.1 )] Pulmonary and Gastroesophageal Hemorrhage [see Warnings and Precautions ( 5.2 )] High-Grade Dysplasia (HGD) in Barrett’s Esophagus (BE) [see Warnings and Precautions ( 5.3 )] Photosensitivity [see Warnings and Precautions ( 5.4 )] Ocular Sensitivity [see Warnings and Precautions ( 5.5 )] Use Before or After Radiotherapy [see Warnings and Precautions ( 5.6 )] Chest Pain [see Warnings and Precautions ( 5.7 )] Airway Obstruction and Respiratory Distress [see Warnings and Precautions ( 5.8 )] Esophageal Strictures [see Warnings and Precautions ( 5.9 )] Thromboembolism [see Warnings and Precautions ( 5.11 )] Most common adverse reactions (>10%) are Esophageal Cancer : Anemia, pleural effusion, pyrexia, constipation, nausea, chest pain, pain, abdominal pain, dyspnea, photosensitivity reaction, pneumonia, vomiting, insomnia, back pain, pharyngitis ( 6.1 ) Obstructing Endobronchial Cancer : Dyspnea, photosensitivity reaction, hemoptysis, pyrexia, cough, pneumonia ( 6.1 ) Superficial Endobronchial Tumors : Exudate, photosensitivity reaction, bronchial obstruction, edema, bronchostenosis ( 6.1 ) High-Grade Dysplasia in Barrett’s Esophagus : Photosensitivity reaction, esophageal stenosis, vomiting, chest pain, nausea, pyrexia, constipation, dysphagia, abdominal pain, pleural effusion, dehydration ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pinnacle Biologics, Inc. at 1-866-248-2039 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Overall Adverse Reaction Profile Systemically induced effects of photodynamic therapy (PDT) with PHOTOFRIN consist of photosensitivity and mild constipation. All patients who receive PHOTOFRIN will be photosensitive and must observe precautions to avoid sunlight and bright indoor light [see Warnings and Precautions ( 5.4 ) ]. Photosensitivity reactions occurred in approximately 20% of cancer patients and in 69% of high-grade dysplasia (HGD) in Barretts esophagus (BE) patients treated with PHOTOFRIN. Typically, these reactions were mostly mild to moderate erythema, but they also included swelling, pruritus, burning sensation, feeling hot, or blisters. In a single study of 24 healthy subjects, some evidence of photosensitivity reactions occurred in all subjects.Other less common skin manifestations were also reported in areas where photosensitivity reactions had occurred, such as increased hair growth, skin discoloration, skin nodule, skin wrinkling and increased skin fragility. These manifestations may be attributable to a pseudoporphyria state (temporary drug-induced cutaneous porphyria). Most toxicities of this therapy are local effects seen in the region of illumination and occasionally in surrounding tissues. The local adverse reactions are characteristic of an inflammatory response induced by the photodynamic effect. A few cases of fluid imbalance have been reported in patients treated with PHOTOFRIN PDT for overtly disseminated intraperitoneal malignancies. Fluid imbalance is an expected PDT-related event. A case of cataracts has been reported in a 51-year-old obese man treated with PHOTOFRIN PDT for HGD in BE. The patient suffered from a PDT response with development of a deep esophageal ulcer. Within two months post PDT, the patient noted difficulty with his distant vision. A thorough eye examination revealed a change in the refractive error that later progressed to cataracts in both eyes. Both of his parents had a history of cataracts in their 70s. Whether PHOTOFRIN directly caused or accelerated a familial...
Drug Interactions
7 DRUG INTERACTIONS Other Photosensitizing Agents : May increase the risk of photosensitivity reaction ( 7.1 ) 7.1 Use with Other Photosensitizing Agents PHOTOFRIN can cause photosensitivity. The concomitant use of PHOTOFRIN with other photosensitizing agents (e.g., tetracyclines, sulfonamides, phenothiazines, sulfonylurea hypoglycemic agents, thiazide diuretics, griseofulvin, and fluoroquinolones) may increase the risk of a photosensitivity reaction. Avoid the concomitant use of PHOTOFRIN with other products known to cause photosensitivity.
Contraindications
4 CONTRAINDICATIONS PHOTOFRIN is contraindicated in patients with porphyria. Photodynamic therapy (PDT) is contraindicated in patients with an existing tracheoesophageal or bronchoesophageal fistula. PDT is contraindicated in patients with tumors eroding into a major blood vessel. PDT is not suitable for emergency treatment of patients with severe acute respiratory distress caused by an obstructing endobronchial lesion because 40 to 50 hours are required between injection with PHOTOFRIN and laser light treatment. PDT is not suitable for patients with esophageal or gastric varices, or patients with esophageal ulcers >1 cm in diameter. Porphyria ( 4 ) Existing tracheoesophageal or bronchoesophageal fistula ( 4 , 5.1 ) Tumors eroding into a major blood vessel ( 4 , 5.2 ) Emergency treatment of patients with severe acute respiratory distress caused by an obstructing endobronchial lesion because 40 to 50 hours are required between injection of PHOTOFRIN and laser light treatment ( 4 ) Esophageal or gastric varices or esophageal ulcers >1 cm in diameter ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on animal studies, PHOTOFRIN may cause embryo-fetal toxicity when administered to a pregnant woman. There are no available data on PHOTOFRIN use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Intraveneous administration of porfimer sodium to pregnant rats and rabbits during the period of organogenesis at dose levels approximately 0.64 times the recommended human dose of PHOTOFRIN based on body surface area (BSA) resulted in increased fetal resorptions, decreased litter size, and reduced fetal weight, but did not cause fetal malformations. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20% respectively. Data Animal Data Intravenous administration of porfimer sodium to pregnant rats for 10 days during the period of organogenesis at dose levels 0.64 times the recommended human dose of PHOTOFRIN based on BSA resulted in maternal and embryo-fetal toxicity resulting in increased resorptions, decreased litter size, delayed ossification, and reduced fetal weight but did not cause major fetal malformations. Intravenous administration of porfimer sodium to pregnant rabbits for 13 days during the period of organogenesis at dose levels 0.65 times the recommended human dose of PHOTOFRIN based on BSA caused maternal toxicity resulting in increased resorptions, decreased litter size, and reduced fetal body weight but did not cause major fetal malformations. Intravenous administration of porfimer sodium to rats for at least 42 days during late pregnancy (post- organogenesis, GD17-PND21) through lactation at dose levels 0.32 times the recommended human dose of PHOTOFRIN based on BSA caused a reversible decrease in growth of offspring. Parturition was unaffected.
Overdosage
10 OVERDOSAGE PHOTOFRIN Overdose There is limited information on overdosages involving PHOTOFRIN. Laser treatment should not be given if an overdose of PHOTOFRIN is administered. In the event of an overdose, instruct patients to protect their eyes and skin from direct sunlight or bright indoor lights for at least 30 days and then test for residual photosensitivity [ see Warnings and Precautions ( 5.4 )] . PHOTOFRIN is not dialyzable. Overdose of Laser Light Following PHOTOFRIN Life-threatening dyspnea has been reported in a patient with a superficial endobronchial tumor who was administered a light dose higher than the recommended dose. Increased symptoms and damage to normal tissue might be expected following an overdose of light. There is no information on overdose of laser light following PHOTOFRIN in patients with esophageal cancer or with high-grade dysplasia in Barrett’s esophagus.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING PHOTOFRIN (porfimer sodium) for Injection is supplied as a lyophilized powder as follows: NDC 76128-155-75, 75 mg single-dose vial. Storage Store at Controlled Room Temperature 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [ see USP Controlled Temperature ]. Spills and Disposal Spills of PHOTOFRIN should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. All contaminated materials should be disposed of in a polyethylene bag in a manner consistent with local regulations. Accidental Exposure PHOTOFRIN is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PHOTOFRIN might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdosage, any overexposed person must be protected from bright light.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.